Heavy-metal derivatives of 1-hydroxy-2-pyridinethiones and method of preparing same



States Uite HEAVY-METAL DERIVATIVES F l-HYDROXY-Z- PYRIDINETHIONES ANDMETHOD OF PREPAR- ING SAME 1 Jack Bernstein and Kathryn A. Losee, NewBrunswick,

N. J., assignors to: 0lin Mathieson, Chemical Corporation, New York, N.;Y., a corporation of Virginia No Drawing. Application November 22,1955,

Serial No. 548,545

8 Claims. (Cl. 260-270) This application is a continuation-in-part ofour parent application, Serial No. 358,542, filed May 29, 1953, nowabandoned.

This invention relates to, and has for its object, the provision of; (A)heavy-metal salts of 1-hydroXy-2(1H)- pyridinethiones (hereinafterreferredto for brevity as l-hydroxy-2-pyridinethiones) of the generalFormula I:

wherein R:is.--hydrogen,-loweralkyl, lower alkoxy or halogen, and n is-apositive integer less than five; and (B) methods of preparing same.

The compounds of this invention can'beprepared by a method whichcomprises interacting a l-hydroxy-2- This tautomerism will not bealluded to hereinafter, it being understood that such tautomeric form(e. g., 2-

, pounds which can be prepared asdisclosed in I. A. C. S.

mercaptopyridine-l-oxide) is included when referring to the compounds ofthis invention either by formula such as I,.or by a name. such as1-hydroXy-2-pyridinethione.-]

Examples .of. utilizable compounds I include the following (inter alia)andsoluble salts thereof:- l-hydroxy- Z-pyridinethione; 1-hydroxy-3(4,5,or 6)-methyl-2-pyridinethione; 1-hydroxy-3(4, 5, n or,6)-ethyl-2-pyridinethione; 1-hydroxy-3(4, 5,,or 6)-n-butyl2-pyridinethione; l-hydroxy (14,15, or.6) -methoxy-Z-pyridinethione;l-hydroxy-3(4, 5,;or. '6)-ethoxy-2-pyridinethione; l-hydroxy- 3(or 5)-bromo=2-pyridinethione; l-hydroxy-S (or 5 chloro=2-,pyridinethione;l-hydroxy-4,6 (or 3 ,6 I or 5, 6) '-dimethyLZ-pyridinethione;1-hydr0Xy-4,6(or 3,6 or 5,6)-diethyl-Z-pyridinethione; l-hydroxy-2(4, 5,or 6)- ethyl- 6(3,4 or 5)-methyl 2-pyridinethione; 1-hydro gy -4,5(or3,6 or 5,6)-dimethoxy-2-pyridiuethione; 1-hydroxy-3,5-dibroma-Z-pyridmethiohe; 1-hydroxy-3,S-dichloro-Z-pyridinethione; 1-hydr oxy-4,5 ,6-trimethyl 2 pyridinethione; andl-hydroxy-3,4,5,6-tetramethyl-2-pyridinethione, The unsubstituted1-hydroxy-2-pyridinethione and the monosubstit-uted=1-hydroxy-2-pyridinethione are known comarsenic).

acetates, sulfates, and halides. When a semi-metal, such,

72, 4362 (1950). The polysubstituted l-hydroxy-Z-pyridinethiones ;.are,; new compounds which can be prepared by, amethod comprising. reactingthe desiredZ-aminopolysubstitutedapyridine. with hydrobromic acid andbro.- mine and reacting the product thus formed withnitrous' acid toyield the corresponding 2-bromo-polysubstitutedpyridine, introducing thel-oxide group by treatment with a peracidysuch as perbenzoic orperacetic acid to.form corresponding2-bromo-polysubstituted-pyridine-1-.

the oxide of the Formula III:

wherein R is lower alkyl, lower alkoxy, or halogen and ture,andtheresulting product is converted toits alkali' metal or ammoniumsalt by alkalization with, a,basesuch as an alkali metal hydroxide orammonium hydroxide or a salt of the alkali metal with a. weak acid (e.g. sodium carbonate). The reaction yields an alkali metal oratnmoniumsalt of a compound of Formula I, wherein njs 2,3, or 4, depending on thedegree of substitution of the starting pyridine reactant.

Suitable heavy-metal compound reactants (II) utilizable in theconversion of compounds of Formula I (or theiralkali'metal or ammoniumsalts) to the heavy-metal salts of this'invention include salts in whichthe heavymetal group is (inter alia) copper, iron, manganese, tin,mercury, cobalt, chromium, lead, gold, cadmium, nickel, silver, zinc,titanium, arsenic, antimony, and bismuth (the term heavy metal, asemployed herein, including the heavy non-metals of metallic character,such as The reactants II may be (inter alia) nitrates,

as arsenic, antimony, or bismuth, is used,'in some instances less thanthe total valence of the element is used in the making of theheavy-metal salt, so that a basic salt is produced as illustrated inExample 9, hereinafter. The following examples are illustrative of, butnot limitative 'of, the invention: 7

EXAMPLE 1 Manganese salt of 1-hydroxy-Z-pyridinethione A solution of0.99 g. (0.005 mole) of manganese chloride tetrahydrate in 50 cc. ofwater is added to a solutionof 1.27 g. (0.01 mole) ofl-hydroxy-Z-pyridine- EXAMPLE 2 Nickel-salt of1-hydr0gen-2-pyridinethione A solution of 1.18 g. 0.005 mole) of nickelchloride hexahydrate in 50 cc. of water is added to a solution ofPatented. Got. 15, 1957.

1.27 g. of 1-hydroxy-Z-pyridinethione in 10 cc. of N sodium hydroxide.The product, a brown solid, precipitates immediately, and is filtered,washed with water, alcohol and ether, and is air-dried. Weight about1.26 g.

EXAMPLE 3 Ferric salt of 1-hydroxy-Z-pyridinethiane A solution of 1.35g. (0.0033 M) of ferric nitrate in 50 cc. of water containingapproximately 10 cc. of 10% nitric acid is added to a solution of 1.27g. of l-hydroxy- Z-pyridinethione in 10 cc. N sodium hydroxide. Theproduct, a blue solid, precipitates immediately, and is filtered, washedwith water, alcohol and ether and airdried. Weight about 1.33 g.

EXAMPLE A 4 Ferrous salt of 1-hydr0xy-2-pyridinethione A solution of0.85 g. (0.005 mole) of FeSO4 (86%) in 50cc. of water containing 15 cc.of 10% sulfuric acid is added to a solution of 1.27 g. of1-hydroxy-2-pyridinethione in 10 cc. of normal sodium hydroxide. Theproduct, a green solid, precipitates, and is filtered, washed withwater, alcohol and ether and air-dried. Weight about 1.15 g.

EXAMPLE 5 Mercaric salt of I-hydr0xy-2-pyridinethi0ne A solution of 1.59g. (0.005 mole) of mercuric acetate in 50 cc. of water is added to asolution of 1.27 g. of 1-hydroxy-2-pyridinethione in cc. of normalsodium hydroxide. The product, a white solid, precipitates and isfiltered, washed with water, alcohol and ether and air-dried. Weightabout 2.13 g.

EXAMPLE 6 Mercuroas salt of I-hydroxy-2-pyridinethi0ne A solution of 2.8g. (0.01 mole) of HgNO3.H2O in 50 cc. of water containing approximatelycc. of 10% nitric acid is added to a solution of 1.27 g. of l-hydroxy-Z-pyridinethione in 10 cc. of normal sodium hydroxide. The product, agray solid, precipitates and is filtered, washed with water, alcohol,and ether and air-dried. Weight about 2.67 g.

EXAMPLE 7 Silver salt 0 I-hydr0xy-2-pyridirzethione A solution of 1.69g. (0.01 mole) of silver nitrate in 50 cc. of water is added to asolution of 1.27 g. of 1- hydroxy-2-pyridinethione in 10 cc. of N sodiumhydroxide. The product, a white solid, forms and is filtered, washedwith water, alcohol and ether and air-dried, weight 2.41 g.

EXAMPLE 8 Auric salt of I-hydroxy-2-pyrzdinethione A solution of 3.03 g.(0.01 mole) of gold chloride in 50 cc. of water is added to a solutionof 3.81 (0.03 mole) of l-hydroxy-2-pyridinethione in 30 cc. of N sodiumhydroxide. The solid which precipitates is filtered, washed with water,alcohol and ether and air-dried.

EXAMPLE 9 Antimonous basic salt of 1-hya'r0xy-2-pyria'inethione Asolution of 0.76 g. (0.0033 mole) of antimony trichloride in 50 cc. ofwater containing approximately 15 cc. of HCl is added to a solution of1.27 g. of 1- hydroxy-Z-pyridinethione in 10 cc. of normal sodiumhydroxide. The product, a white solid, precipitates immediately, and isfiltered, washed with water, alcohol and ether and airdried. Weightabout 1.3 g. (It appears trom analysis that two moles ofl-hydroxy-Z-pyridinethione react with one mole of the antimony com- (Thebismuth and arsenic derivatives are believed to have a correspondingstructure.)

EXAMPLE 10 Antimonic salt of 1-hydroxy-Z-pyridinethione A solution of2.99 g. (0.01 mole) of antimony pentachloride in 100 cc. of watercontaining approximately cc. of 20% EC] is added to a solution of 6.35g. (0.05 mole) of 1-hydroXy-2-pyridinethione in 50 cc. of normal sodiumhydroxide. The solid which precipitates is filtered, washed with water,alcohol and ether and air-dried.

EXAMPLE 11 Cobaltoas salt of 1-hydr0xy-2-pyridinethi0ne A solution of1.46 g. (0.005 mole) of Co(NO3)2.6H2O in 50 cc. of water is added to asolution of 1.27 g. of 1-hydroxy-2-pyridinethione in 10 cc. of N sodiumhydroxide. The product, a gold-colored solid, precipitates and isfiltered, washed with water, alcohol and ether and air-dried. Weightabout 1.35 g.

EXAMPLE 12 Lead salt of I-hydr0xy-2-pyridinethi0ne A solution of 1.66 g.(0.005 mole) of lead nitrate in 50 cc. of water is added to a solutionof 1.27 g. of 1- hydroxy-Z-pyridinethione in 10 cc. of N sodiumhydroxide. The product, a pale yellow solid, precipitates and isfiltered, washed with water, alcohol and ether and air-dried. Weightabout 1.88 g.

a light yellow solid, precipitates and is EXAMPLE 13 Bismuth salt ofI-hydr0xy-2-pyridinethione A solution of 1.62 g. (0.0033 mole) ofBi(NO3)3.5H2O

in 50 cc. of water containing 15 cc. of 10% nitric acid is added to asolution of 1.27 g. of I-hydroxy-Z-pyridinethione in 10 cc. of N sodiumhydroxide. The product, filtered, washed with water, alcohol and etherand air-dried. about 1.69 g.

EXAMPLE l4 Arsenic salt of 1-hydroxy-2-pyridinethione A solution of 1.81g. (0.01 mole) of arsenic trichloride' in 50 cc. of water containingapproximately 20 cc. of

20% HCl is added to a solution of 3.81 g. (0.03 mole) of1-l1ydroxy-2-pyridinethione in 30 cc. of N sodium hydroxide. The solidwhich precipitates is filtered, washed with water, alcohol and ether andair-dried.

EXAMPLE 15 Cupric salt '0) I-hydr0xy-2-pyridinethione A solution of 1.27g. of 1-hydroxy-2-pyridinethione in 15 cc. of alcohol is added to asolution of 1.25 g. (0.005

Weight molel Of jCuSOeSI-I'QO in 100 cc. of water. The product, a darkgreen precipitate; forms immediately and is filtered, washed with water,alcohol and ether. Weight about 1.3 g. a 1

EXAMPLE 16 Zinc salt of 1-hydroxy-2-pyridinethione place of vl-hydroxy2-pyridinethione-in- Example --16, yields the zinc salts ofthecorrespondingG-methyland5-brorno substituted compounds.

EXAMPLE 11 Cadmium salt of 1-hya'roxy 2-pyl idineth i0ite The prod-Asolution of l.83.g. (0.01 mole) of'cadmiurn chloride 7 in. 50 cc.. of,water is-added to ;a solution of 2.54 g; (0.02 mole) of1-hydroXy-2-pyridinethione. in .20 cc. .of normal; sodium hydroxide. Thesolid which precipitates is filtered, washed with water, alcohol andether and air-dried.

EXAMPLE 18 Preparation of 1-hydr0xy-3-ethylf6-methyl 2-pyridinethione. s

(a) 2-brome3-ethyl-6-methylpyriaine.A "solution of 80 g. (0.6 mole) of2-amino-3-ethyl-6-methylpyridine in. 657 cc. of.48 hydrobromic acid istreated Wlthf89 cc.

of bromine and 100 g.; of sodium nitrite according toJ.

Am.v Chem. Soc. 71,,72 (19.49). There is obtained. about 1 80g. (75%)product boiling--at--approximately-9 193- C./ 4 mm.

(b) 2-brom-3-ethyl-6-methylpyridine-l oxide. To *a solution of g- (0.25mole) of 2-br0m-3-methyl-6- methylpyridine in 175 cc. acetic acid isadded g. 40%

peracetic acid. slowly at 10-15" C. After complete addition thereactionis allowed to come to. room temperature and then heated at 4045 C. for16 hours. The acetic acidis removed .under reduced pressure at 60, C.and

the residue poured onto cracked ice. strongly-alkaline with 50% NaOH andextracted with 2 X400 .cc. chloroform. The chloroform is dried-overMgSO4. To the dried solution is added cc. of 3.8 N ethereal hydrogenchloride. The resulting solution is concentrated to 200 cc. on a waterpump and after ,the addition of 200 cc. dry ether, a crystalline solidprecipitates. Thisis filtered and washed with ether. The crude product;weighs about 55 g. (87%) and melts at about 107-108 C. Afterrecrystallization from alcohol-ether the product weighs about 48 g.(76%) and melts at about 110 1113 C.

(c) 1-hydr0xy-3-ethyl-6-methyl-2-pyridinethiane. A solution of 12.6 g.(0.05 mole) of 2brom-3-ethyl-6-methylpyridine-l-oxide, 3.8 g. (0.05mole). ofthiourea and 75 cc. of-absolute-alcoholis refluxed undernitrogen for 16;hours., The alcohol isaremoved and .the residue .pouredinto water and made alkaline with sodium carbonate. The mixture isallowed to standat room temperature for one-half hour, treated withdecolorizing charcoal, filtered} and acidified with 10% HCl. The whitesolid which crystallizes outweighs about 1.2 g. andmelts 81;:

approximately 40-42?. C...

It is then made Ziitc salt=0fI-hydroxy-d-ethyl-fi-methyl-Lpyridinethioneii To a solution of 338mg.(0.002 mole) of 1- hyd roxy-3 ethyl-6-methyl-2-pyridinethione in-10 cc.of alcohol there i ddeda s lu ion-M1288. g- .001 mo e) Q .Z .04- .H2O in50 cc. of water. A gummy precipitant forms which granulates readilyon-,gentle ,warmingpand trituration.

The solid is;filtered;.and washed with water,-.-alcohql,and..

u EXAMPLE 20 Ferric salt of 1-hydr0xy-3-ethyI-6-methyl-Z-pyriiiinethioneA solution of 507 mgr-(0.003 mole) of 1-hydroxy-3- ethyl6-meth-yl;2-pyridinethione ,in 10 ,"CC. 0f alcohol .is added to asolution of 404 mg. (0.001 mole) of in 50 cc. of water plus 10 cc.: of10% nitric acid.'-; A black precipitateforms which is filtered and,washed :with water,

alcohol and. ether Weight ab ut 300 mgr, M. B. approxi.-

mately 135l40 C. (dec.). v

In ..a..similar manner; bysubstituting an equivalent amount of1rhydroxy-3 ethyl-G-methyI-Z-pyridinethione.Y

for the l-hydroxy-Z-pyridinethione inExamples -1, 2, 4 through 15,andll,thecorresponding manganese, nickel, ferrous, .mercuric,.mercurous, silver, auric, antimonous, antimonic,. cobaltous, lead,bismuth, arsenic,- cupric, and cadmium-saltsare .produced, respectively.7

H EXAMPLE 21 Preparation of 1-hydrOxy-4,6-dimethyl-2-pyridinethi0ne (a).2.br.0m0..-.4,6edimethylpyridineePTo -a .solution...of.

91.5 g. of 2-amino-4,6-dimethylpyridine in 850 cc. of 48% z-HBr is addeddropwise 115 cc. of bromine at 0 to 5 C; withvigorous stirring. A thickorange solid forms. After completion of-the addition of bromine, thereaction mixture is treated with a solution of g. of sodium nitrite in:200cc. of' watcr at 0 C. The reaction is then allowed to' come, to roomtemperature, made strongly alkaline by the addition of-approximatelyone-1iter of 50%f'NaOl-I at 10-15 C. and decolorized by the additionof-l00:g.,of sodium'sulfitein 500 cC."H20'-" The reaction mixture issteam distilled and the distillate extracted with 3 500cc. ether. Theether is dried. over MgSO4 and removed. The residue is fraetionated'to,

yield about 64g. ,of produet boih'ng at about 9294 C./ 7 mm.

(b) 2br0m0-4,6-dimethylpyridine 1-oxid e hydr oc hloe ride ;64 g.2-bromo-4,6-dimethylpyridine is dissolved in 200 cc. of acetic acid and100g. of 40%"peracetic acid.

is added keeping the temperature below 15 C. After complete addition,the reaction is allowedto cometo room temperatureand then heated at 45C. for 12hours.

The acetic acid is removed under reduced pressure and the residue pouredonto cracked ice and made strongly alkaline with. 40% KOH.. The1oi1which precipitates is extracted with 3x200 cc. chloroform. Thechloroform is dried over MgSO4 and then dry HCl gas added until acidtoCongo. This solution is concentrated to 250cc. under reduced pressure toyield about 62 g. pIQd lCt, whichmelts at about 157 158 C.(dec.). Afterrecrystallization from absolute alcohol, the product melts at about157'l58 C. (dec.).

(c) 1 hydroxy-4,6-climethyl-2-pyridinethi0ne.-A solution-.of 2.38 g. of2-bromo-4,G-dimethylpyridine l-oxide HCl in 20 cc. of absolute alcoholis added to a solution of 0.76 g. of thiourea in 20 cc. of absolutealcohol. The solution is refluxed for 15 minutes and then concentratedunder reduced pressure. The resulting oil is dissolved in 100 cc. ofwater and solid NazCO; added until the solution is-valkaline. Afterstanding 15 minutes, the solution is-filteredand acidified with 10% HCl.The crystalline solid is, filtered and melts at 105107 C. AfterrecrystalliZatiQn. from 25 cc. aqueous alcohol, the compound melts atabout 108109 C.

'7 EXAMPLE 22 Zinc salt of 1-hydr0xy-4,6-dimethyl 2-pyridinethi0ne tratabulated in Tables I and II, wherein the effectivenessof heavy-metalsalts of compounds of the formula:

were determined.

TABLE L-ANTIBACTERIAL ACTIVITY EXAMPLE 23 Minimum Inhibiting Concen-Ferrtc salt of 1-hydr0xy-4,6-dzmethyl-Z-pyrzdmethtone Compound tratig i(0161733 igmicrograms per g. To a solution of 1.55 g. (0.01 mole) ofl-hydroxy-4,6- dimethyl-Z-pyridinethione in 75 cc. of acetone is added aSalt R Staph. K. BOG solution of 1.38 g. 0.003 mole) of Fe(NO3)3.9HzO inPneum- 150 cc. of water plus 5 cc. of nitric acid. A black precipitateforms immediately. This is filtered, washed as 1 8:83 with water,alcohol and ether. Weight about 950 mg.; 3 301 M. P. about 200 0.(dec.). I g r 3; 30 ;3, In a similar manner, by substituting anequivalent 3.8g 8.812 amount of 1-hydro ry:4,6-dimethyl-2-pyridinethionefor the l-hydroxy-2-pyr1dlnethlone 1n Examples 1, 2, 4 g- 8 8? through15, and 17, the corresponding manganese, nickel, 1 L5 1 ferrous,mercuric, mercurous, silver, auric, antimonous, 15

15 15 0.06 antlmomc, cobaltous lead, bismuth, arsenic, cuprle, and 2 60M3 cadmium salts of 1-hydroXy-4,6-dimethyl-2-pyridinethione 1 areproduced, respectively.

TABLE II.ANTIFUNGAL ACTIVITY Compound MIC g/m1.) Microorganism g 3 5 E E.3 s g 13 g3 Salt R 5 5 s E 33 5% E 5 fie 1:53 a: 3, Es 3.5 E... E3 5.me 1; 5 1:2 5' E E a: 8' 6; a: as: Q 27: .28 61.3 on 23. e 'e' -35 @E"2. 6.5 '"Q =2 3s 33 's a 33 3s s3 33 s 3 3s 3 s 3 33 we we 3e 13 03 33as. 03 6s .3 es .3 on 3.: 1-6

ControL- 8-h dro uino- 122)??? 12.5 3.1 3.1 3.1 1.6 3.1 50 3.1 12.6Cuprie Hydrogen- 3 25 3 6 3 3 25 3 3 0.10 Zinc d 3 6 3 3 3 3 3 3 3 3 0.8Manganese. 1.6 1.6 3.1 0.8 3.1 0.8 1.6 0.8 0.8 3.1 0.3 1.6 0.8 3.1 13 136.3 13+ 1.6 13+ 3.1 3.1 13+ 1.6 13 1.6 1.5 3.1 6.3 1.5 13 13 13+ 6.3 1.513 0.8 6.3 0.8 1.6 3.1 1.6 1.6 6.3 0.3 6.3 3.1 1.6 3.1 0.8 3.1 0.8 1.63.1 1.6 6.3 0.8 1.6 1.6 0.8 3.1 0.8 1.6 0.8 0.8 1.6 0.8 13 0.3 1.6 6.30.8 1.6 0.8 0.8 1.6 3.1 3.1 0.8 13+ 1.6 3.1 1.6 0.3 3.1 0.8 3.1 3.1 3.16.3 3.1 13+ 1.6 3.1 13 1.6 6.3 0.8 3.1 0.8 1.6 3.1 0.3 13+ 0.8 1.6 130.8 6.3 0.3 1.6 50 50 12.5 50 50 100 50 50 100+ 100+ 6. 2 100+ 100+ 100+100+ 100+ 100+ 25 100+ 6.5 100+ 100+ 100 12. 5 6.25 100+ 3.1 50

Examples 18 through 23 are merely illustrative of the Additional invitro tests show that the heavy-metal salts heavy-metal salts ofl-hydroxy-diflower alkyl)-2-pyridineare highly effective in the controlof fungi associated with thiones within the purview of this invention;and other the destruction of cotton fabrics, some of these salts beingdi(lower alkyl)-2-aminopyridines can of course be subfar more effectivethan is the copper salt of 8-hydroxystituted for the2-amino-3-ethyl-6-methylpyridine and 2- quinoline, a standard agent forthe purpose. 'The results amino-4,6-dimethylpyridine starting materialsspecifically of these tests are tabulated in Table III, wherein IDaodisclosed. means the inhibitory dose in parts per million (p. p. m.) Theheavy-metal salts of this invention are active bacfor half of thespecific fungus and ID is the dose for tericides and fungicides asevidenced by the in vitro speccomplete inhibition.

TABLE III Aspergillus Aspergillua Chaetonium Myrothecium Salt ofl-hydroxyniger terreus globosum varrucaria Z-pyridinethione I m) IDmo Iso IDmo IDso I mo IDso IBM a soagsri The s. flthisi nvention canrah refobel servatives (forexample', inle'athenpaperand pai especially inplastics and "fabrics 'to render them proof against mildeworrothenfungusiattack. In theiprotection of fabrics, for-examplewithe-theza salts"ofathis invention, the salt, may be applied to and/orincorporatedinflthfi fabric in' a number ofways." For'example; tliefab'r'ic'may be impregnated-with'the'saltor one'of thdmoietis thereof(as explained hereinafter) as by soaking or spraying. Thus, the fabricmay be impregnated with l-hydroxy-Z- pyridinethione (Formula I) orsoluble salt thereof (e. g. an alkali metal salt) by soaking it in asolution thereof; and the impregnated fabric is then treated with asolution of a soluble compound of the desired heavy-metal. The reverseof this procedure can also be used. Preferably, however, the fabric isfirst treated with an aqueous solution of an alkali metal salt of acompound of Formula I, and then with a substantially water-solubleheavy-metal salt.

Along the same lines, the salts of this invention can also be used asprotective agents for cords and ropes to prevent loss of tensilestrength due to the action of cellulytic fungi. For this purpose, thedesired salt may be sprayed on the cord as an aqueous suspension, or thecord bathed in an aqueous suspension of the given salt.

To show this use of the salts, a test was conducted wherein 4-threadcord was bathed in the salt indicated in Table IV at the designatedconcentration, and the percentage loss (or gain of tensile strength inpounds after fourteen-day exposure to the cellulytic fungi Chaetoniumglobosum and Myrothecium verrucaria compared to that of cord treatedwith the chemical but not exposed to the fungi is reported:

From the above table it can be seen that many of the heavy-metal saltsof the l-hydroxy-2-pyridinethione series are superior to the standardagent, the copper salt of S-hydroxyquinoline in protecting cord fromattack by cellulytic fungi.

One of the most important uses for the salts of this in vention is asplant protective agents, for which purpose they can be used either asfoliage fungicides and bactericides, or as soil fungicides. When used:as foliage fungicides, the salts are most advantageously sprayed on theplants to be treated. A suitable spray can be prepared by wetball-milling the desired salt with water and preferably a wetting agentsuch as a polyoxyalkylene sorbitan higher fatty acid (e. g. Tween 20, apolyoxyethylene sorbitan monolaurate). To demonstrate this use of thesalts of this invention, the effective concentration in parts permillion (ED95) of the salts listed in Table V which prevented 95 percentof the disease symptoms of treated cucumbers and tomatoes wasdetermined. For this test, cucumber and tomato plants were sprayed withan aqueous suspension of the salt and a wetting agent (Tween and thethus-treated plants were then sprayed with a spore suspension ofColletotrichum lagenarium in the case of the cucumbers to initiatefolian anthracnose, and with Alternaria s-olani in the case of tomatoesto initiate early blight.

Tliexesults are summarized Table V, which also cates thatthe salts'haveno phytotoxicity. 1

TABLE V Cucumber Tomatolfiarly r Anthracnose Blight; Salt ofl-hydroxy;-% V

pyrldlnethionm; I H V p EDns" Phyto- E1395" Phyto toxicity toxicity 5 Noinjury-.. 250 No injury. 8 do 125 Do. 14 d0 225 D0. 16 d0 250 Do.

5 (82% control.)

and chemical. To demonstrate this use of the salts of this invention,sterile soil was infested with week old potato dextrose agar platecultures of Rhizoctonia solani and allowed to incubate in greenhouseflats for four or five days. Gallon aliquots of the infested soil and ofsterile non-infested soil were treated with a test chemical. The soilwas treated by spreading the gallon lots in a thin layer, sprinkling thechemical over the surface, and thoroughly mixing the soil and chemical.Each gallon of treated soil was divided in half, and twenty seeds wereplanted in each half gallon of both infested and noninfested soil. Theinfested series served to measure disease control and the non-infestedseries served to measure phytotoxicity. The containers were watered asneeded and observed daily for recording post emergence damping off.Three weeks after treating and seeding final stand counts were made andpreand post-emergence damping-off were calculated. Under theseconditions, the cupric salt of 1-hydroxy-2-pyridinethione in aconcentration of 0.24 g. of salt per gallon of soil was found to protectof cucumber seeds with no injury to the plants and to protect 77% ofcotton seeds with no injury to the plants. Furthermore, the zinc salt oflhydroxy 2-pyridinethione at a concentration of 0.12 g./gal. soil wasfound to protect 60% of cucumber seed with only very slight stunting andthe manganese salt of 1-hydroxy- 2-pyridinethione at the sameconcentration was found to protect 50% of cucumber seeds with only veryslight stunting.

To determine the elfectiveness of the salts against Pythium ultimumincited disease in peas, the experiment was repeated except that thesoil was infested with wheat culture of P. ultimum rather than R. solaniand seeds of garden pea were used. Under these conditions, the followingsalts of l-hydroxy-2-pyridinethione at a concentration of 0.24 gram ofsalt per gallon of soil protected the given percent of peas and in allinstances there was no injury to the plants: cupric salt, 65%; zincsalt, 50%; manganese salt, 78%; and cobalt salt, 62%.

The salts of this invention find further use as agricultural nematocidesand thus when mixed with soil aid in the protection of plants fromnematode damage such as rotting of the attacked parts and adjacenttissue of the plants and the development of galls and other abnormalgrowth.

The invention may be otherwise variously embodied Within the scope ofthe appended claims.

We claim:

1. Heavy-metal salts of 1-hydroxy-2-pyridinethiones of the generalformula wherein R is a member of the class consisting of hydro-;

gen, lo'wer alkyl, lower alkoxy, and halo'gen, and n is'a positiveinteger less than five. j t w 2. Heavy-metal salts of1-hydroxy-2-pyridinethione.

3. Heavy-metal salts of l-hydroxy-diflowef alkyl)- 5- 2-pyridinethione.

4. Zinc salt of l-hydroxy-Z-pyridinethione. 5. Manganese salt of1-hydroxy-2-pyridinethione.

.6. Ferric salt of l-hydrdxy-Z-pyridinethione. 7. Cobaltbus salt of'1-hydroxy-2-pyi-idinethione. 8; Cnpric salt oflvlaydvexyapyridinethione.

I References Cited in the file of this patent UNIIED STATES PATENTS2,429,096 Ladd Oct. 14, 1947 2,686,786

Shaw et a1. Aug. 17, 1954

1. HEAVY-METAL SALTS OF 1-HYDROXY-2-PYRIDINETHIONES OF THE GENERALFORMULA